Date: 2014-04-24
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in the Lancet
Company: Bayer HealthCare (Germany) Onyx Pharmaceuticals (USA)
Product: Nexavar® (sorafenib)
Action
mechanism: oral multi-kinase inhibitor with a distinct profile targeting angiogenic (VEGFR, TIE-2), stromal (PDGFR) and oncogenic (RAF, RET and KIT) receptor tyrosine kinases
Disease: locally advanced or metastatic radioactive iodine-refractory (RAI) differentiated thyroid cancer
Therapeutic area: Cancer - Oncology
Country: International study
Trial
details: The DECISION (stuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine refractory thyrOid caNcer) trial was an international, multicenter, randomized, placebo-controlled study that randomized 417 patients with locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer (papillary, follicular, Hurthle cell and poorly differentiated) who had received no prior chemotherapy, tyrosine kinase inhibitors, monoclonal antibodies that target VEGF or VEGF receptor, or other targeted agents for thyroid cancer. Patients were randomized to receive 400 mg of oral Nexavar® twice daily or matching placebo. At the time of progression, patients receiving placebo had the option to cross over to Nexavar® at the discretion of the investigator, based on the patient\'s clinical status. The primary endpoint of the study was progression-free survival, as defined by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints included overall survival, time to progression, response rate and duration of response. Safety and tolerability were also evaluated. "Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial". Dr Marcia S Brose et al. The Lancet, Volume 384, Issue 9940, Pages 319 - 328, 26 July 2014. doi:10.1016/S0140-6736(14)60421-9. Published Online: 24 April 2014
Latest
news: * On April 2014 24, Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, an Amgen subsidiary, have announced that positive data from the pivotal Phase III DECISION trial of sorafenib (Nexavar®) were published online on April 23rd in The Lancet. These data supported FDA approval of Nexavar® for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine (RAI) treatment in November 2013. Sorafenib has also been submitted for regulatory review to the European Medicines Agency (EMA) for this indication. In November 2013, sorafenib was granted an orphan drug designation for the treatment of follicular and papillary thyroid cancer by the European Commission. In DECISION, sorafenib met the primary endpoint of the study by significantly extending progression-free survival (PFS) compared to placebo (HR 0.59; 95% CI, 0.45-0.76; p<0.0001), representing a 41 percent reduction in the risk of progression or death for patients who received sorafenib compared to placebo-treated patients. The median PFS was 10.8 months in patients treated with sorafenib, compared to 5.8 months in patients receiving placebo. Exploratory subgroup analysis of PFS showed consistent improvement in all pre-specified subgroups, including age, sex, geographical region, histology, sites of metastases and tumor burden. There was no statistically significant difference in overall survival (HR 0.80; 95% CI, 0.54-1.19; p=0.14) and median overall survival had not yet been reached at time of analysis, which was expected due to the post-progression crossover from placebo to open-label sorafenib by the majority (71%) of placebo patients upon progression. A significant improvement of disease control rate (54.1% versus 33.8%, p<0.0001) and of time to progression (HR 0.56; 95% CI, 0.43-0.72; p<0.0001, median: 11.1 months versus 5.7 months) in sorafenib patients versus placebo patients were observed. Additionally, shrinkage of target lesions was seen in a majority of sorafenib-treated patients. Adverse events were consistent with the known sorafenib safety profile. The most common AEs in the sorafenib arm were hand-foot skin reaction, diarrhea, alopecia, rash/desquamation, fatigue, weight loss and hypertension. * On June 2, 2013, Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals have announced positive results from the Phase 3 DECISION trial investigating the use of Nexavar® (sorafenib) tablets in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory differentiated thyroid cancer. Sorafenib significantly extended progression-free survival (PFS), the primary endpoint of the study, compared to placebo. The median PFS was 10.8 months among patients treated with sorafenib, compared to 5.8 months among patients receiving placebo (HR=0.587 [95% CI, 0.454-0.758]; p < 0.0001). PFS was evaluated by an independent radiological review committee using Response Evaluation Criteria in Solid Tumors (RECIST). Safety and tolerability in the study were generally consistent with the known profile of sorafenib. At the time of progression, patients had the option to cross over to open-label sorafenib at the discretion of the investigator; 71% of patients in the placebo arm received open-label sorafenib after progression; 27% of patients in the sorafenib arm received open-label sorafenib after progression. There was no statistically significant difference in overall survival between the treatment arms (HR=0.802 [95% CI, 0.539-1.194]; p=0.138), a secondary endpoint of the trial. Median overall survival has not yet been reached in either arm. The most common treatment-emergent adverse events across all grades occurring in ? 20% of patients taking sorafenib vs. placebo were hand-foot skin reaction (76.3% vs. 9.6%), diarrhea (68.6% vs. 15.3%), alopecia (67.1% vs. 7.7%), rash/desquamation (50.2% vs. 11.5%), fatigue (49.8% vs. 29.4%), weight loss (46.9% vs. 13.9%) hypertension (40.6% vs. 12.4), metabolic/laboratory (35.7% vs. 16.7%), anorexia (31.9% vs. 4.8%),oral mucositis (23.2% vs. 3.3%), pruritis (21.3% and 10.5%) and nausea (20.8% and 11.5%). Treatment-emergent adverse events led to discontinuation in 18.8% of patients who received sorafenib, compared to 3.8% of patients who received placebo. The Phase 3 DECISION data will form the basis for regulatory submissions of sorafenib for the treatment of RAI-refractory differentiated thyroid cancer. Submission of a supplemental New Drug Application (sNDA) in the United States is planned for mid-year 2013, with additional submissions to follow globally. * On January 3, 2013, Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals have announced that a Phase 3 trial of Nexavar® (sorafenib) tablets in patients with locally advanced or metastatic radioactive iodine-refractory (RAI) differentiated thyroid cancer has met its primary endpoint of a statistically significant improvement of progression-free survival. The study, called DECISION, evaluated the efficacy and safety of Nexavar compared to placebo. Adverse events were generally consistent with the known profile for Nexavar®. Data from this study are expected to be presented at an upcoming medical meeting. The companies anticipate that this data will form the basis for regulatory submission of Nexavar® in the treatment of RAI-refractory differentiated thyroid cancer.
